| First Author | Meyer D | Year | 1998 |
| Journal | Blood | Volume | 92 |
| Issue | 11 | Pages | 3997-4002 |
| PubMed ID | 9834201 | Mgi Jnum | J:87127 |
| Mgi Id | MGI:2683747 | Doi | 10.1182/blood.v92.11.3997.423k52_3997_4002 |
| Citation | Meyer D, et al. (1998) FcgammaRIII (CD16)-deficient mice show IgG isotype-dependent protection to experimental autoimmune hemolytic anemia. Blood 92(11):3997-4002 |
| abstractText | In autoimmune hemolytic anemia (AIHA), there is accumulating evidence for an involvement of FcgammaR expressed by phagocytic effector cells, but demonstration of a causal relationship between individual FcgammaRs and IgG isotypes for disease development is lacking. Although the relevance of IgG isotypes to human AIHA is limited, we could show a clear IgG isotype dependency in murine AIHA using pathogenic IgG1 (105-2H) and IgG2a (34-3C) autoreactive anti-red blood cell antibodies in mice defective for FcgammaRIII, and comparing the clinical outcome to those in wild-type mice. FcgammaRIII-deficient mice were completely resistent to the pathogenic effects of 105-2H monoclonal antibody, as shown by a lack of IgG1-mediated erythrophagocytosis in vitro and in vivo. In addition, the IgG2a response by 34-3C induced a less severe but persistent AIHA in FcgammaRIII knock-out mice, as documented by a decrease in hematocrit. Blocking studies indicated that the residual anemic phenotype induced by 34-3C in the absence of FcgammaRIII reflects an activation of FcgammaRI that is normally coexpressed with FcgammaRIII on macrophages. Together these results show that the pathogenesis of AIHA through IgG1-dependent erythrophagocytosis is exclusively mediated by FcgammaRIII and further suggest that FcgammaRI, in addition to FcgammaRIII, contributes to this autoimmune disease when other IgG isotypes such as IgG2a are involved. |
